thioredoxin; Several proteins, such as protein disulfide isomerase, have two or more copies of a domain closely related to thioredoxin. This model is designed to recognize authentic thioredoxin, a small protein that should be hit exactly once by this model. Any protein that hits once with a score greater than the second (per domain) trusted cutoff may be taken as thioredoxin. [Energy metabolism, Electron transport]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   6 LNDSNFKGEIESG--LTLVDFWAPWCGPCRMIAPVVEEIASQYEGKVKVGKVNVDDNQQTAMQFRVMSIPTLILFKDGQP 83
Cdd:TIGR01068   1 LTDANFDETIASSdkPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKE 80

                          90       100
                  ....*....|....*....|.
gi 1906190757  84 VEGVVGAQPKRAFEALLDKHL 104
Cdd:TIGR01068  81 VDRSVGALPKAALKQLINKNL 101

Thioredoxin; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond. Some members with only the active site are not separated from the noise.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   5 ELNDSNFKGEI--ESGLTLVDFWAPWCGPCRMIAPVVEEIASQYEGKVKVGKVNVDDNQQTAMQFRVMSIPTLILFKDGQ 82
Cdd:pfam00085   4 VLTDANFDEVVqkSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQ 83

                          90       100
                  ....*....|....*....|
gi 1906190757  83 PVEGVVGAQPKRAFEALLDK 102
Cdd:pfam00085  84 PVDDYVGARPKDALAAFLKA 103

thioredoxin; Several proteins, such as protein disulfide isomerase, have two or more copies of a domain closely related to thioredoxin. This model is designed to recognize authentic thioredoxin, a small protein that should be hit exactly once by this model. Any protein that hits once with a score greater than the second (per domain) trusted cutoff may be taken as thioredoxin. [Energy metabolism, Electron transport]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   6 LNDSNFKGEIESG--LTLVDFWAPWCGPCRMIAPVVEEIASQYEGKVKVGKVNVDDNQQTAMQFRVMSIPTLILFKDGQP 83
Cdd:TIGR01068   1 LTDANFDETIASSdkPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKE 80

                          90       100
                  ....*....|....*....|.
gi 1906190757  84 VEGVVGAQPKRAFEALLDKHL 104
Cdd:TIGR01068  81 VDRSVGALPKAALKQLINKNL 101

Thioredoxin; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond. Some members with only the active site are not separated from the noise.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   5 ELNDSNFKGEI--ESGLTLVDFWAPWCGPCRMIAPVVEEIASQYEGKVKVGKVNVDDNQQTAMQFRVMSIPTLILFKDGQ 82
Cdd:pfam00085   4 VLTDANFDEVVqkSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQ 83

                          90       100
                  ....*....|....*....|
gi 1906190757  83 PVEGVVGAQPKRAFEALLDK 102
Cdd:pfam00085  84 PVDDYVGARPKDALAAFLKA 103

thioredoxin TrxA;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   2 KPMELNDSNFKGEI--ESGLTLVDFWAPWCGPCRMIAPVVEEIASQYEGKVKVGKVNVDDNQQTAMQFRVMSIPTLILFK 79
Cdd:PRK09381    4 KIIHLTDDSFDTDVlkADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFK 83

                          90       100
                  ....*....|....*....|....*.
gi 1906190757  80 DGQPVEGVVGAQPKRAFEALLDKHLA 105
Cdd:PRK09381   84 NGEVAATKVGALSKGQLKEFLDANLA 109

Protein Disulfide Isomerase (PDIa) family, redox active TRX domains; composed of eukaryotic proteins involved in oxidative protein folding in the endoplasmic reticulum (ER) by acting as catalysts and folding assistants. Members of this family include PDI and PDI-related proteins like ERp72, ERp57 (or ERp60), ERp44, P5, PDIR, ERp46 and the transmembrane PDIs. PDI, ERp57, ERp72, P5, PDIR and ERp46 are all oxidases, catalyzing the formation of disulfide bonds of newly synthesized polypeptides in the ER. They also exhibit reductase activity in acting as isomerases to correct any non-native disulfide bonds, as well as chaperone activity to prevent protein aggregation and facilitate the folding of newly synthesized proteins. These proteins usually contain multiple copies of a redox active TRX (a) domain containing a CXXC motif, and may also contain one or more redox inactive TRX-like (b) domains. Only one a domain is required for the oxidase function but multiple copies are necessary for the isomerase function. The different types of PDIs may show different substrate specificities and tissue-specific expression, or may be induced by stress. PDIs are in their reduced form at steady state and are oxidized to the active form by Ero1, which is localized in the ER through ERp44. Some members of this family also contain a DnaJ domain in addition to the redox active a domains; examples are ERdj5 and Pfj2. Also included in the family is the redox inactive N-terminal TRX-like domain of ERp29.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   5 ELNDSNFKGEI-ESGLTLVDFWAPWCGPCRMIAPVVEEIASQYE--GKVKVGKVNVDDNQQTAMQFRVMSIPTLILFKDG 81
Cdd:cd02961     2 ELTDDNFDELVkDSKDVLVEFYAPWCGHCKALAPEYEKLAKELKgdGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNG 81

PDIa family, endoplasmic reticulum protein 46 (ERp46) subfamily; ERp46 is an ER-resident protein containing three redox active TRX domains. Yeast complementation studies show that ERp46 can substitute for protein disulfide isomerase (PDI) function in vivo. It has been detected in many tissues, however, transcript and protein levels do not correlate in all tissues, suggesting regulation at a posttranscriptional level. An identical protein, named endoPDI, has been identified as an endothelial PDI that is highly expressed in the endothelium of tumors and hypoxic lesions. It has a protective effect on cells exposed to hypoxia.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   2 KPMELNDSNFKGEIESGLTLVDFWAPWCGPCRMIAPVVEEIASQYE---GKVKVGKVNVDDNQQTAMQFRVMSIPTLILF 78
Cdd:cd03005     1 GVLELTEDNFDHHIAEGNHFVKFFAPWCGHCKRLAPTWEQLAKKFNnenPSVKIAKVDCTQHRELCSEFQVRGYPTLLLF 80

                          90       100
                  ....*....|....*....|.
gi 1906190757  79 KDGQPVEGVVGaqpKRAFEAL 99
Cdd:cd03005    81 KDGEKVDKYKG---TRDLDSL 98

PDIa family, P5 subfamily; composed of eukaryotic proteins similar to human P5, a PDI-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is located in the endoplasmic reticulum (ER) and displays both isomerase and chaperone activities, which are independent of each other. Compared to PDI, the isomerase and chaperone activities of P5 are lower. The first cysteine in the CXXC motif of both redox active domains in P5 is necessary for isomerase activity. The P5 gene was first isolated as an amplified gene from a hydroxyurea-resistant hamster cell line. The zebrafish P5 homolog has been implicated to play a critical role in establishing left/right asymmetries in the embryonic midline. Some members of this subfamily are P5-like proteins containing only one redox active TRX domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1906190757   5 ELNDSNFKGE-IES-GLTLVDFWAPWCGPCRMIAPVVEEIASQYEGKVKVGKVNVDDNQQTAMQFRVMSIPTLILFKDG 81
Cdd:cd03001     4 ELTDSNFDKKvLNSdDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIKVFGAG 82

TRX-like protein A (TxlA) family; TxlA was originally isolated from the cyanobacterium Synechococcus. It is found only in oxygenic photosynthetic organisms. TRX is a small enzyme that participate in redox reactions, via the reversible oxidation of an active site dithiol present in a CXXC motif. Disruption of the txlA gene suggests that the protein is involved in the redox regulation of the structure and function of photosynthetic apparatus. The plant homolog (designated as HCF164) is localized in the chloroplast and is involved in the assembly of the cytochrome b6f complex, which takes a central position in photosynthetic electron transport.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757  20 TLVDFWAPWCGPCRMIAPVVEEIASQYEGKVKVGKVNVDDN--QQTAMQFRVMSIPTLILF-KDGQPVEGVVGAQPKRAF 96
Cdd:cd02950    23 TLVEFYADWCTVCQEMAPDVAKLKQKYGDQVNFVMLNVDNPkwLPEIDRYRVDGIPHFVFLdREGNEEGQSIGLQPKQVL 102

                  ....*
gi 1906190757  97 EALLD 101
Cdd:cd02950   103 AQNLD 107

PDIa family, endoplasmic reticulum protein 38 (ERp38) subfamily; composed of proteins similar to the P5-like protein first isolated from alfalfa, which contains two redox active TRX (a) domains at the N-terminus, like human P5, and a C-terminal domain with homology to the C-terminal domain of ERp29, unlike human P5. The cDNA clone of this protein (named G1) was isolated from an alfalfa cDNA library by screening with human protein disulfide isomerase (PDI) cDNA. The G1 protein is constitutively expressed in all major organs of the plant and its expression is induced by treatment with tunicamycin, indicating that it may be a glucose-regulated protein. The G1 homolog in the eukaryotic social amoeba Dictyostelium discoideum is also described as a P5-like protein, which is located in the endoplasmic reticulum (ER) despite the absence of an ER-retrieval signal. G1 homologs from Aspergillus niger and Neurospora crassa have also been characterized, and are named TIGA and ERp38, respectively. Also included in the alignment is an atypical PDI from Leishmania donovani containing a single a domain, and the C-terminal a domain of a P5-like protein from Entamoeba histolytica.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   4 MELNDSNFKGEI--ESGLTLVDFWAPWCGPCRMIAPVVEEIASQYEG--KVKVGKVNVDD-NQQTAMQFRVMSIPTLILF 78
Cdd:cd02998     3 VELTDSNFDKVVgdDKKDVLVEFYAPWCGHCKNLAPEYEKLAAVFANedDVVIAKVDADEaNKDLAKKYGVSGFPTLKFF 82

                  ....*....
gi 1906190757  79 --KDGQPVE 85
Cdd:cd02998    83 pkGSTEPVK 91

protein disulfide isomerase, eukaryotic; This model represents eukaryotic protein disulfide isomerases retained in the endoplasmic reticulum (ER) and closely related forms. Some members have been assigned alternative or additional functions such as prolyl 4-hydroxylase and dolichyl-diphosphooligosaccharide-protein glycotransferase. Members of this family have at least two protein-disulfide domains, each similar to thioredoxin but with the redox-active disulfide in the motif PWCGHCK, and an ER retention signal at the extreme C-terminus (KDEL, HDEL, and similar motifs).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   5 ELNDSNFKGEIESG-LTLVDFWAPWCGPCRMIAPVVEEIA---SQYEGKVKVGKVNVDDNQQTAMQFRVMSIPTLILFKD 80
Cdd:TIGR01130   5 VLTKDNFDDFIKSHeFVLVEFYAPWCGHCKSLAPEYEKAAdelKKKGPPIKLAKVDATEEKDLAQKYGVSGYPTLKIFRN 84

                  ...
gi 1906190757  81 GQP 83
Cdd:TIGR01130  85 GED 87

Thioredoxin domain-containing protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   4 MELNDSNFKG--EIESGLT----LVDFWAPWCGPCRMIAPVVEEIASQYEGKVKVGKVNVDDNQQTAMQFRVMSIPTLIL 77
Cdd:PTZ00443   33 VLLNDKNFEKltQASTGATtgpwFVKFYAPWCSHCRKMAPAWERLAKALKGQVNVADLDATRALNLAKRFAIKGYPTLLL 112

                  ....*
gi 1906190757  78 FKDGQ 82
Cdd:PTZ00443  113 FDKGK 117

TRX domain, novel NADPH thioredoxin reductase (NTR) family; composed of fusion proteins found only in oxygenic photosynthetic organisms containing both TRX and NTR domains. The TRX domain functions as a protein disulfide reductase via the reversible oxidation of an active center dithiol present in a CXXC motif, while the NTR domain functions as a reductant to oxidized TRX. The fusion protein is bifunctional, showing both TRX and NTR activities, but it is not an independent NTR/TRX system. In plants, the protein is found exclusively in shoots and mature leaves and is localized in the chloroplast. It is involved in plant protection against oxidative stress.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757  19 LTLVDFWAPWCGPCRMIAPVVEEIASQYEGKVKVGKVNVDDNQQTAMQFRVMSIPTLILFKDGQPVEGVVGAQPKRAFEA 98
Cdd:cd02949    15 LILVLYTSPTCGPCRTLKPILNKVIDEFDGAVHFVEIDIDEDQEIAEAAGIMGTPTVQFFKDKELVKEISGVKMKSEYRE 94

                  ...
gi 1906190757  99 LLD 101
Cdd:cd02949    95 FIE 97

PDIa family, endoplasmic reticulum protein 44 (ERp44) subfamily; ERp44 is an ER-resident protein, induced during stress, involved in thiol-mediated ER retention. It contains an N-terminal TRX domain, similar to that of PDIa, with a CXFS motif followed by two redox inactive TRX-like domains, homologous to the b and b' domains of PDI. The CXFS motif in the N-terminal domain allows ERp44 to form stable reversible mixed disulfides with its substrates. Through this activity, ERp44 mediates the ER localization of Ero1alpha, a protein that oxidizes protein disulfide isomerases into their active form. ERp44 also prevents the secretion of unassembled cargo protein with unpaired cysteines. It also modulates the activity of inositol 1,4,5-triphosphate type I receptor (IP3R1), an intracellular channel protein that mediates calcium release from the ER to the cytosol.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   5 ELNDSNFKGEIES-GLTLVDFWAPWCGPCRMIAPVVEEIASQY------EGKVKVGKVNVDDNQQTAMQFRVMSIPTLIL 77
Cdd:cd02996     5 SLTSGNIDDILQSaELVLVNFYADWCRFSQMLHPIFEEAAAKIkeefpdAGKVVWGKVDCDKESDIADRYRINKYPTLKL 84

                          90       100
                  ....*....|....*....|....
gi 1906190757  78 FKDGQPVEGVVGAQpkRAFEALLD 101
Cdd:cd02996    85 FRNGMMMKREYRGQ--RSVEALAE 106

PDIa family, TMX subfamily; composed of proteins similar to the TRX-related human transmembrane protein, TMX. TMX is a type I integral membrane protein; the N-terminal redox active TRX domain is present in the endoplasmic reticulum (ER) lumen while the C-terminus is oriented towards the cytoplasm. It is expressed in many cell types and its active site motif (CPAC) is unique. In vitro, TMX reduces interchain disulfides of insulin and renatures inactive RNase containing incorrect disulfide bonds. The C. elegans homolog, DPY-11, is expressed only in the hypodermis and resides in the cytoplasm. It is required for body and sensory organ morphogeneis. Another uncharacterized TRX-related transmembrane protein, human TMX4, is included in the alignment. The active site sequence of TMX4 is CPSC.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1906190757   5 ELNDSNFKgEIESGLTLVDFWAPWCGPCRMIAPVVEEIASQYEG-KVKVGKVNVDDNQQTAMQFRVMSIPTLILFKDG 81
Cdd:cd02994     5 ELTDSNWT-LVLEGEWMIEFYAPWCPACQQLQPEWEEFADWSDDlGINVAKVDVTQEPGLSGRFFVTALPTIYHAKDG 81

PDIa family, C-terminal TRX domain (a') subfamily; composed of the C-terminal redox active a' domains of PDI, ERp72, ERp57 (or ERp60) and EFP1. PDI, ERp72 and ERp57 are endoplasmic reticulum (ER)-resident eukaryotic proteins involved in oxidative protein folding. They are oxidases, catalyzing the formation of disulfide bonds of newly synthesized polypeptides in the ER. They also exhibit reductase activity in acting as isomerases to correct any non-native disulfide bonds, as well as chaperone activity to prevent protein aggregation and facilitate the folding of newly synthesized proteins. PDI and ERp57 have the abb'a' domain structure (where a and a' are redox active TRX domains while b and b' are redox inactive TRX-like domains). PDI also contains an acidic region (c domain) after the a' domain that is absent in ERp57. ERp72 has an additional a domain at the N-terminus (a"abb'a' domain structure). ERp57 interacts with the lectin chaperones, calnexin and calreticulin, and specifically promotes the oxidative folding of glycoproteins, while PDI shows a wider substrate specificity. ERp72 associates with several ER chaperones and folding factors to form complexes in the ER that bind nascent proteins. EFP1 is a binding partner protein of thyroid oxidase, which is responsible for the generation of hydrogen peroxide, a crucial substrate of thyroperoxidase, which functions to iodinate thyroglobulin and synthesize thyroid hormones.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1906190757  21 LVDFWAPWCGPCRMIAPVVEEIASQYEG--KVKVGKVNVDDNQQTAMQFrVMSIPTLILFKDG 81
Cdd:cd02995    22 LVEFYAPWCGHCKALAPIYEELAEKLKGddNVVIAKMDATANDVPSEFV-VDGFPTILFFPAG 83

TlpA-like family, DsbE (also known as CcmG and CycY) subfamily; DsbE is a membrane-anchored, periplasmic TRX-like reductase containing a CXXC motif that specifically donates reducing equivalents to apocytochrome c via CcmH, another cytochrome c maturation (Ccm) factor with a redox active CXXC motif. Assembly of cytochrome c requires the ligation of heme to reduced thiols of the apocytochrome. In bacteria, this assembly occurs in the periplasm. The reductase activity of DsbE in the oxidizing environment of the periplasm is crucial in the maturation of cytochrome c.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1906190757   5 ELNDSNFKGeiesGLTLVDFWAPWCGPCRMIAPVVEEIASQyeGKVKVGKVNVDDNQQTAMQF 67
Cdd:cd03010    17 TLTSADLKG----KPYLLNVWASWCAPCREEHPVLMALARQ--GRVPIYGINYKDNPENALAW 73

protein disulfide isomerase, eukaryotic; This model represents eukaryotic protein disulfide isomerases retained in the endoplasmic reticulum (ER) and closely related forms. Some members have been assigned alternative or additional functions such as prolyl 4-hydroxylase and dolichyl-diphosphooligosaccharide-protein glycotransferase. Members of this family have at least two protein-disulfide domains, each similar to thioredoxin but with the redox-active disulfide in the motif PWCGHCK, and an ER retention signal at the extreme C-terminus (KDEL, HDEL, and similar motifs).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   9 SNFKgEI---ESGLTLVDFWAPWCGPCRMIAPVVEEIASQY---EGKVKVGKVNVDDNQQTAmqFRVMSIPTLILFKDGQ 82
Cdd:TIGR01130 354 KNFD-EIvldETKDVLVEFYAPWCGHCKNLAPIYEELAEKYkdaESDVVIAKMDATANDVPP--FEVEGFPTIKFVPAGK 430

                          90       100
                  ....*....|....*....|...
gi 1906190757  83 PVEGVV--GAQPKRAFEALLDKH 103
Cdd:TIGR01130 431 KSEPVPydGDRTLEDFSKFIAKH 453

periplasmic protein thiol:disulfide oxidoreductases, DsbE subfamily; Involved in the biogenesis of c-type cytochromes as well as in disulfide bond formation in some periplasmic proteins. [Protein fate, Protein folding and stabilization]

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1906190757  15 IESGLTLVDFWAPWCGPCRMIAPVVEEIASQyegKVKVGKVNVDDNQQTAMQF 67
Cdd:TIGR00385  61 TQGKPVLLNVWASWCPPCRAEHPYLNELAKQ---GLPIVGVDYKDDRQNAIKF 110

Thioredoxin-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757  20 TLVDFWAPWCGPCRMIAPVVEE---IASQYEGKVKVGKVNVD--DNQQTAMQ-----------FRVMSIPTLILFkDGQ- 82
Cdd:pfam13098   7 VLVVFTDPDCPYCKKLKKELLEdpdVTVYLGPNFVFIAVNIWcaKEVAKAFTdilenkelgrkYGVRGTPTIVFF-DGKg 85

                          90
                  ....*....|....*...
gi 1906190757  83 PVEGVVGAQPKRAFEALL 100
Cdd:pfam13098  86 ELLRLPGYVPAEEFLALL 103

disulphide isomerase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757  21 LVDFWAPWCGPCRMIAPVVEEIASQYE--GKVKVGKVNVDDNQQTAMQFRVMSIPTLILFKDGQ----PVEGvvgaqpKR 94
Cdd:PTZ00102  379 LLEIYAPWCGHCKNLEPVYNELGEKYKdnDSIIVAKMNGTANETPLEEFSWSAFPTILFVKAGErtpiPYEG------ER 452

                          90
                  ....*....|..
gi 1906190757  95 AFEAL---LDKH 103
Cdd:PTZ00102  453 TVEGFkefVNKH 464

PDIa family, PDIR subfamily; composed of proteins similar to human PDIR (for Protein Disulfide Isomerase Related). PDIR is composed of three redox active TRX (a) domains and an N-terminal redox inactive TRX-like (b) domain. Similar to PDI, it is involved in oxidative protein folding in the endoplasmic reticulum (ER) through its isomerase and chaperone activities. These activities are lower compared to PDI, probably due to PDIR acting only on a subset of proteins. PDIR is preferentially expressed in cells actively secreting proteins and its expression is induced by stress. Similar to PDI, the isomerase and chaperone activities of PDIR are independent; CXXC mutants lacking isomerase activity retain chaperone activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   6 LNDSNFKGEI-ESGLTLVDFWAPWCGPCRMIAPVVEEIAS--QYEGKVKVGKVNV--DDNQQTAMQFRVMSIPTLILFKD 80
Cdd:cd02997     5 LTDEDFRKFLkKEKHVLVMFYAPWCGHCKKMKPEFTKAATelKEDGKGVLAAVDCtkPEHDALKEEYNVKGFPTFKYFEN 84

                          90       100
                  ....*....|....*....|
gi 1906190757  81 GQPVEGVVGAQPKRAFEALL 100
Cdd:cd02997    85 GKFVEKYEGERTAEDIIEFM 104

PDIa family, 5'-Adenylylsulfate (APS) reductase subfamily; composed of plant-type APS reductases containing a C-terminal redox active TRX domain and an N-terminal reductase domain which is part of a superfamily that includes N type ATP PPases. APS reductase catalyzes the reduction of activated sulfate to sulfite, a key step in the biosynthesis of sulfur-containing metabolites. Sulfate is first activated by ATP sulfurylase, forming APS, which can be phosphorylated to 3'-phosphoadenosine-5'-phosphosulfate (PAPS). Depending on the organism, either APS or PAPS can be used for sulfate reduction. Prokaryotes and fungi use PAPS, whereas plants use both APS and PAPS. Since plant-type APS reductase uses glutathione (GSH) as its electron donor, the C-terminal domain may function like glutaredoxin, a GSH-dependent member of the TRX superfamily. The flow of reducing equivalents goes from GSH -> C-terminal TRX domain -> N-terminal reductase domain -> APS. Plant-type APS reductase shows no homology to that of dissimilatory sulfate-reducing bacteria, which is an iron-sulfur flavoenzyme. Also included in the alignment is EYE2 from Chlamydomonas reinhardtii, a protein required for eyespot assembly.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757  12 KGEIESGLTLVDFWAPWCGPCRMIAPVVEEIASQYEG-KVKVGKVNVD-DNQQTAMQ-FRVMSIPTLILF 78
Cdd:cd02993    16 KGERRNQSTLVVLYAPWCPFCQAMEASYEELAEKLAGsNVKVAKFNADgEQREFAKEeLQLKSFPTILFF 85

TRX domain, TRX and NDP-kinase (NDPK) fusion protein family; most members of this group are fusion proteins which contain one redox active TRX domain containing a CXXC motif and three NDPK domains, and are characterized as intermediate chains (ICs) of axonemal outer arm dynein. Dyneins are molecular motors that generate force against microtubules to produce cellular movement, and are divided into two classes: axonemal and cytoplasmic. They are supramolecular complexes consisting of three protein groups classified according to size: dynein heavy, intermediate and light chains. Axonemal dyneins form two structures, the inner and outer arms, which are attached to doublet microtubules throughout the cilia and flagella. The human homolog is the sperm-specific Sptrx-2, presumed to be a component of the human sperm axoneme architecture. Included in this group is another human protein, TRX-like protein 2, a smaller fusion protein containing one TRX and one NDPK domain, which is also associated with microtubular structures. The other members of this group are hypothetical insect proteins containing a TRX domain and outer arm dynein light chains (14 and 16kDa) of Chlamydomonas reinhardtii. Using standard assays, the fusion proteins have shown no TRX enzymatic activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   7 NDSNFKGEIES-GLTLVDFWAPWCGPCRMIAPVVEEIasqyegKVKVGKVNVD------DNQQTAMQFRVMSIPTLILFK 79
Cdd:cd02948     6 NQEEWEELLSNkGLTVVDVYQEWCGPCKAVVSLFKKI------KNELGDDLLHfataeaDTIDTLKRYRGKCEPTFLFYK 79

                          90
                  ....*....|..
gi 1906190757  80 DGQPVEGVVGAQ 91
Cdd:cd02948    80 NGELVAVIRGAN 91

5'-adenylylsulfate reductase, thioredoxin-independent; This enzyme, involved in the assimilation of inorganic sulfate, is closely related to the thioredoxin-dependent PAPS reductase of Bacteria (CysH) and Saccharomyces cerevisiae. However, it has its own C-terminal thioredoxin-like domain and is not thioredoxin-dependent. Also, it has a substrate preference for 5'-adenylylsulfate (APS) over 3'-phosphoadenylylsulfate (PAPS) so the pathway does not require an APS kinase (CysC) to convert APS to PAPS. Arabidopsis thaliana appears to have three isozymes, all able to complement E. coli CysH mutants (even in backgrounds lacking thioredoxin or APS kinase) but likely localized to different compartments in Arabidopsis. [Central intermediary metabolism, Sulfur metabolism]

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1906190757  21 LVDFWAPWCGPCRMIAPVVEEIASQYEGK-VKVGKVNVDDNQQ--TAMQFRVMSIPTLILFKDGQP 83
Cdd:TIGR00424 375 LVVLYAPWCPFCQAMEASYLELAEKLAGSgVKVAKFRADGDQKefAKQELQLGSFPTILFFPKHSS 440

OST3 / OST6 family, transporter family; The proteins in this family are part of a complex of eight ER proteins that transfers core oligosaccharide from dolichol carrier to Asn-X-Ser/Thr motifs. This family includes both OST3 and OST6, each of which contains four predicted transmembrane helices. Disruption of OST3 and OST6 leads to a defect in the assembly of the complex. Hence, the function of these genes seems to be essential for recruiting a fully active complex necessary for efficient N-glycosylation. These proteins are also thought to be novel Mg2+ transporters.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   2 KPMELNDSNFKgEIESGL----TLVDFWAPW----CGPCRMIAPVVEEIASQY-------EGKVKVGKVNVDDNQQTAMQ 66
Cdd:pfam04756  12 GVIKLNDSNYK-RLLSGPrdysVVVLLTALDprfgCQLCREFQPEFELVAKSWfkdhkagSSKLFFATLDFDDGKDVFQS 90

                          90
                  ....*....|..
gi 1906190757  67 FRVMSIPTLILF 78
Cdd:pfam04756  91 LGLQTAPHLLLF 102

Thioredoxin domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1906190757  29 CGPCRMIAPVVEEIASQYEGKVKVgkVNVDDNQQtAMQFRVMSIPTLILfkDGQPVegVVGAQPKRAF 96
Cdd:pfam13192   5 CPKCPQLEKAVKEAAAELGIDAEV--EKVTDFPE-IAKYGVMSTPALVI--NGKVV--SSGKVPSEEE 65

TRX family, chloroplastic drought-induced stress protein of 32 kD (CDSP32); CDSP32 is composed of two TRX domains, a C-terminal TRX domain which contains a redox active CXXC motif and an N-terminal TRX-like domain which contains an SXXS sequence instead of the redox active motif. CDSP32 is a stress-inducible TRX, i.e., it acts as a TRX by reducing protein disulfides and is induced by environmental and oxidative stress conditions. It plays a critical role in plastid defense against oxidative damage, a role related to its function as a physiological electron donor to BAS1, a plastidic 2-cys peroxiredoxin. Plants lacking CDSP32 exhibit decreased photosystem II photochemical efficiencies and chlorophyll retention compared to WT controls, as well as an increased proportion of BAS1 in its overoxidized monomeric form.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   4 MELNDSNFKGEiESGLTLVDFWAPWCGPCRMIAPVVEEIaSQYEGKVKVGKVNVDDNQQTaMQF----RVMSIPTLILFK 79
Cdd:cd02985     3 VEELDEALKKA-KGRLVVLEFALKHSGPSVKIYPTMVKL-SRTCNDVVFLLVNGDENDST-MELcrreKIIEVPHFLFYK 79

                          90
                  ....*....|...
gi 1906190757  80 DGQPVEGVVGAQP 92
Cdd:cd02985    80 DGEKIHEEEGIGP 92

Phosducin (Phd)-like family; composed of Phd and Phd-like proteins (PhLP), characterized as cytosolic regulators of G protein functions. Phd and PhLPs specifically bind G protein betagamma (Gbg)-subunits with high affinity, resulting in the solubilization of Gbg from the plasma membrane and impeding G protein-mediated signal transduction by inhibiting the formation of a functional G protein trimer (G protein alphabetagamma). Phd also inhibits the GTPase activity of G protein alpha. Phd can be phosphorylated by protein kinase A and G protein-coupled receptor kinase 2, leading to its inactivation. Phd was originally isolated from the retina, where it is highly expressed and has been implicated to play an important role in light adaptation. It is also found in the pineal gland, liver, spleen, striated muscle and the brain. The C-terminal domain of Phd adopts a thioredoxin fold, but it does not contain a CXXC motif. Phd interacts with G protein beta mostly through the N-terminal helical domain. Also included in this family is a PhLP characterized as a viral inhibitor of apoptosis (IAP)-associated factor, named VIAF, that functions in caspase activation during apoptosis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1906190757   5 ELNDSNFKGEIE----SGLTLVDFWAPWCGPCRMIAPVVEEIASQYeGKVKVGKVNVDdNQQTAMQFRVMSIPTLILFKD 80
Cdd:cd02957     8 EISSKEFLEEVTkaskGTRVVVHFYEPGFPRCKILDSHLEELAAKY-PETKFVKINAE-KAFLVNYLDIKVLPTLLVYKN 85

                  ....*....
gi 1906190757  81 GQPVEGVVG 89
Cdd:cd02957    86 GELIDNIVG 94

Redoxin; This family of redoxins includes peroxiredoxin, thioredoxin and glutaredoxin proteins.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1906190757   9 SNFKGeiesGLTLVDFWAP-WCGPCRMIAPVVEEIASQYEGK-VKVGKVNVDDNQQTAMQF 67
Cdd:pfam08534  24 SDFKG----KKVVLNFWPGaFCPTCSAEHPYLEKLNELYKEKgVDVVAVNSDNDAFFVKRF 80